Summary: The laboratory of Dr. Verthelyi has been newly created this year. It is focused on identification and characterization of modulators of the innate immune response as they relate to potential therapies for infection with agents of bioterrorism. Current areas of development include the use of synthetic CpG oligodeoxynucleotides (ODN) type D as well as novel DNA sequences that act on Toll-like receptor 9 (TLR 9) expressed by dendritic and B cells resulting in improved antigen uptake/presentation by antigen presenting calls, and the secretion of polyreactive Ig, chemokines and cytokines by B cells, NK cells, dendritic cells, and monocytes. To assert protection, the laboratory utilizes models of infection with Leishmania major and Tacaribe virus, a new world Arenavirus, in mice and non-human primates. This work not only has applications in the area of Bioterrorism, but also in reducing the susceptibility of immunosuppressed subjects to opportunistic infections. Special emphasis is placed on studies addressing the safety and immunogenecity of CpG ODN to support the regulatory efforts in this area. This work is partly funded by a CBER Bioterrorism Initiative Grant.